Mechanistic Study of Novel Whitening Agents: Insights from Molecular Dynamics, Molecular Docking, and Network Pharmacology

In this study, we systematically investigated the mechanism of action of a novel skin-whitening active compound (Compound identifier: SCHEMBL14462430, hereafter referred to as Compound X) using molecular docking, molecular dynamics simulations, and network pharmacology approaches. Molecular docking results demonstrated that Compound X exhibits significant binding interactions with tyrosinase, a key target in skin whitening, with a binding free energy of -7.8 kcal/mol, indicating favorable binding affinity. Molecular dynamics simulations further validated the stability of the Compound X-TYR complex, revealing low flexibility and high structural stability throughout the simulation. The persistent presence of key hydrogen bonds suggested robust dynamic binding activity of Compound X. Additionally, integrated network pharmacology analysis and Western blot experiments revealed that Compound X likely regulates melanogenesis by inhibiting the phosphorylation of p38 protein in the Mitogen-Activated Protein Kinase signaling pathway. This study not only provides a promising candidate molecule for the development of skin-whitening agents but also establishes a theoretical foundation for further exploration of the mechanisms underlying skin-whitening compounds.